Depression of myocardial ATPase activity by plasma obtained during positive end-expiratory pressure

Dogs treated with 15 cm H2O positive end-expiratory pressure (PEEP) invariably show a decrease in cardiac output (CO). Plasma that is obtained from PEEP-treated dogs and applied to an isometrically contracting rat papillary muscle results in a significant depression of the peak developed tension. The present study evaluates the nature of the circulating negative inotropic agent with respect to its action on the coupling of myocardial energy production and contraction. PEEP plasma was found to depress Ca++-ATPase activity (P less than 0.025) when incubated with cardiac subfractions obtained from dog and rat myofibrils, sarcolemma, and sarcoplasmic reticulum. No change in Mg++-ATPase activity was observed. The declines in Ca++-ATPase activity correlate significantly with decreases in left ventricular stroke work, stroke volume, and CO during PEEP treatment. The decrease in Ca++-ATPase with PEEP plasma also correlates with a decrease in developed tension of a rat papillary muscle bathed with PEEP plasma. There were no changes in CO in animals who were simply anesthetized; plasma from these animals did not alter developed tension or ATPase. These observations suggest that PEEP plasma and serum contain a negative inotropic agent(s) that may reduce contractility by Ca++-ATPase inhibition.